{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:15:58Z","timestamp":1780467358504,"version":"3.54.1"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Tubal reanastomosis is an alternative option for women seeking fertility after sterilization. Thus, anastomosis healing quality and peri-tubal adhesions play a crucial role. TISSEEL\u00ae fibrin sealant may enhance tissue repair and reduce foreign-body reaction. We evaluated the effect of TISSEEL\u00ae, used alone or with sutures, on anastomotic healing and adhesion formation in a rat uterine horn model. Materials and Methods: Thirty female Wistar rats were randomized to Suture, TISSEEL\u00ae, or Suture + TISSEEL\u00ae groups (n = 10 each). After bilateral uterine horn transection, reanastomosis was performed with sutures alone, fibrin sealant alone, or combined sutures and sealant. On postoperative day 14, reanastomosis segments were collected for blinded histologic assessment and evaluation of modified Ehrlich\u2013Hunt score parameters (inflammation, fibrosis, neovascularization and collagen production). Intra-abdominal adhesions were also macroscopically assessed. Results: Two animals died perioperatively and 56 uterine horns were included in the final analysis (Suture n = 18, TISSEEL\u00ae\u00a0n = 18, Suture + TISSEEL\u00ae\u00a0n = 20). The distribution of inflammation and fibrosis severity grades, as assessed by the modified Ehrlich\u2013Hunt scoring system, did not differ significantly between the study groups (p = 0.208 and p = 0.652, respectively). In contrast, high-grade neovascularization (grades 3\u20134) was more common in TISSEEL\u00ae groups (77.8% TISSEEL\u00ae, 80.0% Suture + TISSEEL\u00ae, 33.3% Suture, p = 0.004), while increased collagen deposition was also more common in the TISSEEL\u00ae groups (p = 0.011), after binary analysis. Severe adhesions were more common in the Suture group (66.7% vs. 11.1% in the TISSEEL\u00ae group and 30.0% in the Suture + TISSEEL\u00ae group, p = 0.037). Conclusions: TISSEEL\u00ae, alone or as an adjunct to sutures, improves neovascularization and collagen production and is associated with milder adhesions without increased inflammation or fibrosis. The use of fibrin sealant TISSEEL\u00ae may be a useful tool in tubal reconstructive surgery.<\/jats:p>","DOI":"10.3390\/medicina62020333","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T13:33:50Z","timestamp":1770384830000},"page":"333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Effect of TISSEEL\u00ae on the Healing Process of Uterine Horn Reanastomosis in an Experimental Animal Model"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0160-7755","authenticated-orcid":false,"given":"Dimitrios","family":"Papageorgiou","sequence":"first","affiliation":[{"name":"Department of Gynecology, Athens Naval and Veterans Hospital, 11521 Athens, Greece"},{"name":"Laboratory of Experimental Surgery and Surgical Research \u201cN.S. Christeas\u201d, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilios","family":"Pergialiotis","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Unit of Gynecologic Oncology, \u201cAlexandra\u201d Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Salakos","sequence":"additional","affiliation":[{"name":"School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stylianos","family":"Kykalos","sequence":"additional","affiliation":[{"name":"Second Department of Propaedeutic Surgery, \u201cLaikon\u201d General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1399-0301","authenticated-orcid":false,"given":"Kalliroi","family":"Goula","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u201cAlexandra\u201d Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Kontzoglou","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Surgery and Surgical Research \u201cN.S. Christeas\u201d, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Second Department of Propaedeutic Surgery, \u201cLaikon\u201d General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","unstructured":"United Nations (2023, February 27). World Family Planning 2022: Meeting the Changing Needs for Family Planning: Contraceptive Use by Age and Method. United Nations. Available online: https:\/\/www.un.org\/development\/desa\/pd\/sites\/www.un.org.development.desa.pd\/files\/files\/documents\/2023\/Feb\/undesa_pd_2022_world-family-planning.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0140-6736(22)00936-9","article-title":"Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"400","author":"Haakenstad","year":"2022","journal-title":"Lancet"},{"key":"ref_3","unstructured":"Daniels, K., and Abma, J.C. (2020). Current Contraceptive Status Among Women Aged 15\u201349: United States, 2017\u20132019, NCHS Data Brief, No. 388."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/AOG.0000000000004692","article-title":"Risk of sterilization regret and age: An analysis of the National Survey of Family Growth, 2015\u20132019","volume":"139","author":"Danvers","year":"2022","journal-title":"Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Godin, P.A., Syrios, K., Rege, G., Demir, S., Charitidou, E., and Wery, O. (2019). Laparoscopic reversal of tubal sterilization: A retrospective study over 135 cases. Front. Surg., 5.","DOI":"10.3389\/fsurg.2018.00079"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ejogrb.2023.10.017","article-title":"Microsurgical anastomosis of the fallopian tubes after tubal ligation: A systematic review and meta-analysis","volume":"291","author":"Sastre","year":"2023","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1177\/0300060517709815","article-title":"Pregnancy outcome of laparoscopic tubal reanastomosis: Retrospective results from a single clinical centre","volume":"45","author":"Karayalcin","year":"2017","journal-title":"J. Int. Med. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Practice Committee of the American Society for Reproductive Medicine (2021). Role of tubal surgery in the era of assisted reproductive technology: A committee opinion. Fertil. Steril., 115, 1143\u20131150.","DOI":"10.1016\/j.fertnstert.2021.01.051"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1093\/humupd\/dmx003","article-title":"Tubal anastomosis after previous sterilization: A systematic review","volume":"23","author":"Chua","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_10","unstructured":"(2025, November 04). TISSEEL [Fibrin Sealant]\u2014Product Information. Available online: https:\/\/www.baxter.com\/healthcare-professionals\/surgical-care\/tisseel-fibrin-sealant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"203943","DOI":"10.1155\/2014\/203943","article-title":"Fibrin sealant: The only approved hemostat, sealant, and adhesive\u2014A laboratory and clinical perspective","volume":"2014","author":"Spotnitz","year":"2014","journal-title":"ISRN Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"659","DOI":"10.21873\/invivo.11820","article-title":"The effect of TISSEEL\u00ae on colorectal anastomosis healing process in a diabetic animal experimental model","volume":"34","author":"Stergios","year":"2020","journal-title":"In Vivo"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.4103\/njcp.njcp_306_17","article-title":"Effect of fibrin glue or suture on leakage in patients undergoing laparoscopic sleeve gastrectomy","volume":"21","author":"Usta","year":"2018","journal-title":"Niger. J. Clin. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12976","DOI":"10.3748\/wjg.v21.i45.12976","article-title":"Endoscopic fibrin sealant closure of duodenal perforation after endoscopic retrograde cholangiopancreatography","volume":"21","author":"Yang","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1159\/000516827","article-title":"The effect of TISSEEL\u2122 on confined bowel perforation: An experimental study","volume":"62","author":"Frountzas","year":"2021","journal-title":"Eur. Surg. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Fatehi Hassanabad, A., Zarzycki, A.N., Jeon, K., Dundas, J.A., Vasanthan, V., Deniset, J.F., and Fedak, P.W.M. (2021). Prevention of post-operative adhesions: A comprehensive review of present and emerging strategies. Biomolecules, 11.","DOI":"10.3390\/biom11071027"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Papageorgiou, D., Pergialiotis, V., Sapantzoglou, I., Sivylla Bikouvaraki, E., Salakos, N., Kykalos, S., and Kontzoglou, K. (2026). The Effect of Fibrin Sealants on Tubal Reanastomosis: A Comprehensive Review of the Literature. J. Pers. Med., 16.","DOI":"10.3390\/jpm16010012"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4103\/0976-500X.119726","article-title":"How to calculate sample size in animal studies?","volume":"4","author":"Charan","year":"2013","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.blre.2014.09.003","article-title":"Fibrinolysis and the control of blood coagulation","volume":"29","author":"Chapin","year":"2015","journal-title":"Blood Rev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nikolaou, C., Frountzas, M., Schizas, D., Pergialiotis, V., Kapetanakis, E.I., Kontzoglou, K., Perrea, D.N., Koniaris, E., Kykalos, S., and Iliopoulos, D. (2024). Could fibrin sealants (TISSEEL\u2122) be effective in the management of burn injuries? A histopathological study in rats. Med. Sci., 12.","DOI":"10.3390\/medsci12040075"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lin, L.-X., Yuan, F., Zhang, H.-H., Liao, N.-N., Luo, J.-W., and Sun, Y.-L. (2017). Evaluation of surgical anti-adhesion products to reduce postsurgical intra-abdominal adhesion formation in a rat model. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172088"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e201900801","DOI":"10.1590\/s0102-865020190080000001","article-title":"The effect of fibrin glue in preventing staple-line leak after sleeve gastrectomy: An experimental study in rats","volume":"34","author":"Ozdenkaya","year":"2019","journal-title":"Acta Cir. Bras."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Barac, S., Jiga, L.P., Rata, A., Sas, I., Onofrei, R.R., and Ionac, M. (2020). Role of reconstructive microsurgery in tubal infertility in young women. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051300"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1093\/oxfordjournals.humrep.a019510","article-title":"Peritoneal healing after fibrin glue application: A comparative study in a rat model","volume":"11","author":"Evrard","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1007\/s00404-011-2097-1","article-title":"A review of the problematic adhesion prophylaxis in gynaecological surgery","volume":"285","author":"Hirschelmann","year":"2012","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.3748\/wjg.v17.i41.4545","article-title":"Pathophysiology and prevention of postoperative peritoneal adhesions","volume":"17","author":"Arung","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3892\/etm.2025.12847","article-title":"Tissue adhesion after surgical interventions (review)","volume":"29","author":"Sturm","year":"2025","journal-title":"Exp. Ther. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10029-011-0834-9","article-title":"Histologic evaluation of absorbable and non-absorbable barrier coated mesh secured to the peritoneum with fibrin sealant in a New Zealand white rabbit model","volume":"15","author":"Jenkins","year":"2011","journal-title":"Hernia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1007\/s00464-012-2154-2","article-title":"The use of novel hemostatic sealant (Tisseel) in laparoscopic myomectomy: A case\u2013control study","volume":"26","author":"Angioli","year":"2012","journal-title":"Surg. Endosc."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mayrhofer-Schmid, M., Aman, M., Panayi, A.C., Raasveld, F.V., Kneser, U., Eberlin, K.R., Harhaus, L., and B\u00f6cker, A. (2024). Fibrin glue coating limits scar tissue formation around peripheral nerves. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073687"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40902-021-00290-x","article-title":"Comparative study of bone regeneration using fibrin sealant with xenograft in rabbit sinus: Pilot study","volume":"43","author":"Choi","year":"2021","journal-title":"Maxillofac. Plast. Reconstr. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons (2013). Pathogenesis, consequences, and control of peritoneal adhesions in gynecologic surgery: A committee opinion. Fertil. Steril., 99, 1550\u20131555.","DOI":"10.1016\/j.fertnstert.2013.02.031"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bayer, I.S. (2022). Advances in fibrin-based materials in wound repair: A review. Molecules, 27.","DOI":"10.3390\/molecules27144504"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.2147\/IJN.S124671","article-title":"A review of fibrin and fibrin composites for bone tissue engineering","volume":"12","author":"Noori","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Diller, R.B., and Tabor, A.J. (2022). The role of the extracellular matrix (ECM) in wound healing: A review. Biomimetics, 7.","DOI":"10.3390\/biomimetics7030087"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mathew-Steiner, S.S., Roy, S., and Sen, C.K. (2021). Collagen in wound healing. Bioengineering, 8.","DOI":"10.3390\/bioengineering8050063"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1067\/maj.2001.120423","article-title":"The effect of fibrin sealant on the healing of laser-resurfaced skin","volume":"21","author":"Eby","year":"2001","journal-title":"Aesthet. Surg. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8449","DOI":"10.1021\/acsabm.5c01083","article-title":"Platelet-rich fibrin (PRF)-polymer composites for wound healing: Macromolecular synergies, structural design, and therapeutic efficacy","volume":"8","author":"Alizadeh","year":"2025","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/j.1524-475X.2011.00740.x","article-title":"Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation","volume":"19","author":"Roy","year":"2011","journal-title":"Wound Repair Regen."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"221","DOI":"10.21873\/invivo.12694","article-title":"Beneficiary effect of fibrin glue on healing of ileoileal anastomoses in rats","volume":"36","author":"Gerogiannis","year":"2022","journal-title":"In Vivo"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1001\/archfaci.5.5.399","article-title":"The effect of two sealants (FloSeal and Tisseel) on fasciocutaneous flap revascularization","volume":"5","author":"Jorgensen","year":"2003","journal-title":"Arch. Facial Plast. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s10456-012-9287-8","article-title":"An in vivo neovascularization assay for screening regulators of angiogenesis and assessing their effects on pre-existing vessels","volume":"15","author":"Kilarski","year":"2012","journal-title":"Angiogenesis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.fertnstert.2005.07.1337","article-title":"Effects of fibrin sealant on single-layer uterine incision closure in the New Zealand white rabbit","volume":"85","author":"Peacock","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1093\/humupd\/dml061","article-title":"Prevention of adhesions in gynaecological endoscopy","volume":"13","author":"Nappi","year":"2007","journal-title":"Hum. Reprod. Update"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10856-024-06780-4","article-title":"Biochemical and biomechanical characterization of an autologous protein-based fibrin sealant for regenerative medicine","volume":"35","author":"Anitua","year":"2024","journal-title":"J. Mater. Sci. Mater. Med."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/2\/333\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T14:00:11Z","timestamp":1770386411000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/2\/333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["medicina62020333"],"URL":"https:\/\/doi.org\/10.3390\/medicina62020333","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}